The major thrust of this study is to elucidate the molecular genetics of neoplastic transformation of normal tissues and the isolation and function of two biological modifiers in the cellular defense mechanism. Two experimental systems were used: 1) Two rat leukemia helper viruses - a) KSV(RHHV) originally isolated in this laboratory and b) WR-RaLV, a wild rat tumor virus, and 2) Interleukin 2 (IL-2), a T-cell product, and a lymphokine, produced by rat spleen cells (predominantly macrophages). Multidisciplinary approaches involving nucleic acid and protein chemistry, recombinant DNA, and tissue culture were employed. We have earlier completed extensive morphological, biological, biochemical and immunological characterizations and the genomic maps of these retroviruses. Our current interests focus on the molecular mechanisms involved in the evolution of a transforming DNA sequence through the recombination between a RaLV DNA sequence and rat endogenous DNA sequence, c-src. Our total research efforts are concentrated on: 1) Restriction endonuclease mapping, 2) Heteroduplex analysis of conservation and divergency in nucleotide sequences, 3) Microinjection of RaLV total and subgenomic DNA sequences for DNA transduction analysis, 4) Nucleotide sequence of RaLV genomic DNA and nucleotide sequence(s) of RaLV subgenomic fragment(s) active in recombination with cellular c-src, 5a) Isolation and purification of IL-2 and of a lymphokine produced through the interaction of macrophages with lymphocytes, 5b) Immediate and long term effects of IL-2 on T-lymphocytes and natural killer cells in cellular defense mechanism, and the function of the lymphokine in the differentiation of cytotoxic T-lymphocyte (CTL) precursors into CTL, 5c) The involvement of this lymphokine in the networks and circuits which regulate the immune surveillance of tumor growth.